Hydroxychloroquine is associated with impaired interferon-alpha and tumor necrosis factor-alpha production by plasmacytoid dendritic cells in systemic lupus erythematosus Full Text
Arthritis Research & Therapy, 06/29/2012
Sacre K et al. – Treatment with hydroxychloroquine (HCQ) is associated with impaired ability of Plasmacytoid dendritic cells (pDCs) from subjects with systemic lupus erythematosus (SLE) to produce IFN–alpha and TNF–alpha upon stimulation with TLR–9 and TLR–7 agonists.Methods
- Peripheral blood mononuclear cells (PBMCs) from SLE subjects treated or not with HCQ and from healthy controls were stimulated with the TLR–9 agonist, CpG oligodeoxynucleotides (CpG–A ODN)–2216, and the TLR–7 agonist, imiquimod.
- The proportion of monocytes, B cells, myeloid dendritic cells, pDCs, and natural killer (NK) cells producing IFN–alpha and TNF–alpha was then analyzed by multiparameter flow cytometry.
- After TLR–9/7 stimulation in both SLE and healthy subjects, significant production of IFN–alpha and TNF–alpha was only observed in pDCs.
- TLR–7 and TLR–9 induced IFN–alpha and TNF–alpha production by pDCs from subjects with SLE was decreased relative to that found in controls (TLR–9/IFN–alpha, P<0.0001; TLR–9/TNF–alpha P<0.0001; TLR–7/TNF–alpha P=0.01).
- TLR–9 and TLR–7 induced IFN–alpha and TNF–alpha production by pDCs was severely impaired in 36% (TLR–9) and 33% (TLR–7) of SLE subjects.
- In almost all cases, these subjects were being treated with HCQ (HCQ vs. no HCQ: impaired TLR–9/IFN–alpha, P=0.0003; impaired TLR–7/IFN–alpha, P=0.07; impaired TLR–9/TNF–alpha, P<0.009; impaired TLR–7/TNF–alpha, P<0.01).